Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.
While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009865 |
| _version_ | 1829496410875101184 |
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| author | Paul A Dabisch Jennifer Biryukov Katie Beck Jeremy A Boydston Jaleal S Sanjak Artemas Herzog Brian Green Gregory Williams John Yeager Jordan K Bohannon Brian Holland David Miller Amy L Reese Denise Freeburger Susan Miller Tammy Jenkins Sherry Rippeon James Miller David Clarke Emmanuel Manan Ashley Patty Kim Rhodes Tina Sweeney Michael Winpigler Owen Price Jason Rodriguez Louis A Altamura Heather Zimmerman Alec S Hail Victoria Wahl Michael Hevey |
| author_facet | Paul A Dabisch Jennifer Biryukov Katie Beck Jeremy A Boydston Jaleal S Sanjak Artemas Herzog Brian Green Gregory Williams John Yeager Jordan K Bohannon Brian Holland David Miller Amy L Reese Denise Freeburger Susan Miller Tammy Jenkins Sherry Rippeon James Miller David Clarke Emmanuel Manan Ashley Patty Kim Rhodes Tina Sweeney Michael Winpigler Owen Price Jason Rodriguez Louis A Altamura Heather Zimmerman Alec S Hail Victoria Wahl Michael Hevey |
| author_sort | Paul A Dabisch |
| collection | DOAJ |
| description | While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation. |
| first_indexed | 2024-12-16T07:30:52Z |
| format | Article |
| id | doaj.art-70d970fd34504da2bf0a8a2ab2464f2c |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-16T07:30:52Z |
| publishDate | 2021-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-70d970fd34504da2bf0a8a2ab2464f2c2022-12-21T22:39:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-08-01178e100986510.1371/journal.ppat.1009865Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.Paul A DabischJennifer BiryukovKatie BeckJeremy A BoydstonJaleal S SanjakArtemas HerzogBrian GreenGregory WilliamsJohn YeagerJordan K BohannonBrian HollandDavid MillerAmy L ReeseDenise FreeburgerSusan MillerTammy JenkinsSherry RippeonJames MillerDavid ClarkeEmmanuel MananAshley PattyKim RhodesTina SweeneyMichael WinpiglerOwen PriceJason RodriguezLouis A AltamuraHeather ZimmermanAlec S HailVictoria WahlMichael HeveyWhile evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.https://doi.org/10.1371/journal.ppat.1009865 |
| spellingShingle | Paul A Dabisch Jennifer Biryukov Katie Beck Jeremy A Boydston Jaleal S Sanjak Artemas Herzog Brian Green Gregory Williams John Yeager Jordan K Bohannon Brian Holland David Miller Amy L Reese Denise Freeburger Susan Miller Tammy Jenkins Sherry Rippeon James Miller David Clarke Emmanuel Manan Ashley Patty Kim Rhodes Tina Sweeney Michael Winpigler Owen Price Jason Rodriguez Louis A Altamura Heather Zimmerman Alec S Hail Victoria Wahl Michael Hevey Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. PLoS Pathogens |
| title | Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. |
| title_full | Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. |
| title_fullStr | Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. |
| title_full_unstemmed | Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. |
| title_short | Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. |
| title_sort | seroconversion and fever are dose dependent in a nonhuman primate model of inhalational covid 19 |
| url | https://doi.org/10.1371/journal.ppat.1009865 |
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